过表达肿瘤坏死因子-α诱导蛋白8家族样蛋白2基因诱导大鼠心脏移植免疫耐受的研究

摘要

Objective A study of wether overexpress tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2) gene can affect the recipients' autoimmune regulation and allograft rejection,and to explore the possibility of the gene induce immune tolerance and its specific mechanism of action in rats.Methods Construct a gene vector of rat,s TIPE2 gene,let it overexpress TIPE2 gene in the rat heart transplantation models,observe wether it can prolong the donor heart,s mean survival time,and detect the changes of some related indicators.Results The survival time of donor heart in each groups:group A:(9.0 ± 1.6) d;group B:(26.3 ±3.8) d;group C:(33.4 ±3.5) d;group D:(48.0 ±6.6) d;group E:(28.8 ± 6.1) d;the survival time of donor heart in was significantly longer than the control group,the difference was statistically significant (P ＜ 0.05);The percentage of CD4 + CD25 + regulatory T cells (Tregs) in each groups:groups A:(1.70 ±0.66)％;group B:(6.42 ± 1.17)％;group C:(9.38 ± 1.13) ％;group D:(31.34 ± 2.23) ％;group E:(1.70 ± 0.72) ％.The percentage of CD4 + CD25 + Tregs in experimental group was significantly higher than the control group,the difference was statistically significant (P ＜ 0.05);Compare to group A,B,C,E,The expression of interleukin (IL)-2,tumor necrosis factor (TNF)-α,interferon (INF)-γin group D was Significantly lower,and the expression of IL-4 and IL-10 was significantly higher.There are significant differences in the levels of cytokines with the control group (P ＜ 0.05).Conclusion TIPE2 play an important role in the induction of immune tolerance in heart transplantation.%目的 观察过表达肿瘤坏死因子-α诱导蛋白8家族样蛋白2(TIPE2)基因能否影响受体自身免疫调节和移植免疫排斥反应,并探讨该基因诱导受体大鼠产生免疫耐受的可能性以及其具体作用机制.方法 构建大鼠TIPE2基因载体,使其在大鼠心脏移植模型受体中过表达TIPE2,观察其能否延长供心存活时间,并检测相关指标的变化.结果 供心存活时间:A组:(9.0±1.6)d;B组:(26.3±3.8)d;C组:(33.4±3.5)d;D组:(48.0±6.6)d;E组:(28.8±6.1)d.实验组供心存活时间较对照组明显延长,差异有统计学意义(P＜0.05);CD4+ CD25+调节性T细胞(Treg)比例:A组:(1.70±0.66)％;B组:(6.42±1.17)％;C组:(9.38±1.13)％;D组:(31.34±2.23)％;E组:(1.70±0.72)％.实验组CD4+ CD25+ Treg细胞较对照组明显升高,差异有统计学意义(P＜0.05);与A、B、C、E组相比,D组受体大鼠外周血中白细胞介素(IL)-2、肿瘤坏死因子-α(TNF-α)、干扰素(IFN)-γ表达明显降低,而IL-4、IL-10表达明显升高,差异有统计学意义(P＜0.05).结论 TIPE2在诱导心脏移植免疫耐受中发挥重要作用.